Suppression of B cell response was shown to be mediated by regulatory T cells functioning through two distinct pathways distinguishable by the involvement of different Lyt-defined T cell subpopulations. Both pathways were MHC-restricted and antigen-specific in their activation requirements. An Lyt 1+2- population functioned through an antigen non-specific effector pathway requiring the participation of an Lyt 1-2+ unprimed T cell. An Lyt 1-2+ T cell functioned through an antigen-specific and MHC restricted effector pathway without requirement for participation of additional T cells. Cloned lines of T cells were derived which function as suppressors of MHC-restricted T cell-dependent antibody responses. These cloned T cells express an Lytl+2- L3T4+ phenotype and proliferate in response to specific antigen plus the appropriate I-A or I-E encoded product. Clone T suppressors inhibit responses of heterogeneous T helper cells and B cells in an MHC-restricted and antigen-specific manner. These cloned suppressor cells are also able to inhibit response mediated by cloned T helper cells in the absence of other T cells, indicating that they can function as direct effectors of suppression. A series of autoreactive T cell clones was also generated which proliferate in response to syngeneic I-A or I-E products without apparent involvement of foreign antigen. Certain of these autoreactive T cells functioned as T helper (TH) cells to activate antibody response by B cells. Autoreacitve TH cells functioned through two distinct pathways: one pathway was polyclonal and MHC unrestricted and dependent upon antigen-specific triggering of responding B cells. It was demonstrated that the optimal antibody responses generated by cloned antigen-specific TH cells were substantialy augmented by populations of unprimed Lyt 1+2- T cells. These T augmenting (TA) cells were MHC-restricted in their ability to cooperate with cloned TH cells.